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In this study, we extended our previously developed, anatomically realistic, three-dimensional thermoregulatory virtual human model to more comprehensively predict changes in core body temperature and skin temperature of peripheral body regions (dorsum hand, fingertip, face, dorsum foot, and toe-tip) and the cheek under extreme cold-air temperatures down to \u221240.0\u00a0\u00b0C and wind speeds ranging from 0.1 to 3.0\u00a0m\u00b7s\n                    <jats:sup>\u22121<\/jats:sup>\n                    . To assess model performance, we computed the root mean square error (RMSE) between model predictions and experimental data as well as the fraction of model predictions that lie within two standard errors of the mean experimental data from eight cold-air exposure studies involving 75 unique subjects. Overall, we observed a reasonable agreement between model predictions and the experimental measurements, with average RMSEs of about 0.2\u00a0\u00b0C for core body temperature, 0.5 to 1.8\u00a0\u00b0C for mean skin, 1.6 to 2.7\u00a0\u00b0C for fingertip, 1.2 to 3.5\u00a0\u00b0C for toe-tip, and 2.1 to 2.7\u00a0\u00b0C for cheek skin temperature. As such, the extended model can serve as a valuable tool to inform the development of guidelines to help mitigate the risk of cold-related injuries during prolonged exposures to extreme-cold environments.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-57039-7","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T10:15:53Z","timestamp":1783764953000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A 3-D whole-body human thermoregulatory model to simulate extreme cold stress"],"prefix":"10.1038","volume":"16","author":[{"given":"Manpreet","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lahcen","family":"Akerkouch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret C.","family":"Morrissey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Szymanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica M.","family":"Filep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Langan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Casa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaques","family":"Reifman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"57039_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1080\/23328940.2024.2408059","volume":"12","author":"L Klous","year":"2024","unstructured":"Klous, L. et al. 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